chapter 6.1 and 6.2: introduction to enzymes chem 7784 biochemistry professor bensley
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Chapter 6.1 and 6.2: Introduction to Enzymes
CHEM 7784
Biochemistry
Professor Bensley
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CHAPTER 6.1 and 6.2 Introduction to Enzymes and How
Enzymes Work
– Physiological significance of enzymes– Origin of catalytic power of enzymes– Chemical mechanisms of catalysis
Today’s Objectives: (To learn and understand the)
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What are Enzymes?
• Enzymes are catalytically active biological macromolecules
• Most enzymes are globular proteins, however some RNA (ribozymes, and ribosomal
RNA) also catalyze reactions
• Study of enzymatic processes is the oldest field of biochemistry, dating back to late 1700s
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Why Biocatalysis?• Higher reaction rates• Greater reaction specificity• Milder reaction conditions• Capacity for regulation
COO
OH
O COO
COO
O COO
NH2
OOCCOO
O
OH
OH
COO
NH2
COO
-
-
-
-
-
-
--
Chorismate mutase
• Metabolites have many potential pathways of decomposition
• Enzymes make the desired one most favorable
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Quiz Question 29
In order to function properly, some enzymes require the presence of an additional chemical component such
as inorganic ions (Zn2+ or Fe2+). These inorganic ions are known as
for enzymes.
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Quiz Question 30
Chymotrypsin is an enzyme that cleaves peptide bonds. It most likely, therefore, belongs to which class of enzymes?
a)Transferases b) Ligases
c) Isomerases d) Hydrolases
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Classes of enzymes
1. Oxidoreductases = catalyze oxidation-reduction reactions (Transfer of electrons) (NADH)
2. Transferases = catalyze transfer of functional groups from one molecule to another.
3. Hydrolases = catalyze hydrolytic cleavage (transfer of functional groups to water)
4. Lyases = catalyze removal of a group from or addition of a group to a double bond, or other cleavages involving electron rearrangement.
5. Isomerases = catalyze intermolecular rearrangement.
6. Ligases = catalyze reactions in which two molecules are joined.
Enzymes named for the substrates and type of reaction
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E + S ES E + Pk1
k-1
k2
k-2
E S+ E S E + P
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Rate Acceleration
• The enzyme lowers the activation barrier compared to the uncatalyzed aqueous reaction
• In theory, the enzyme may also facilitate the tunneling through the barrier. This may be important for electrons.
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How to Lower G?
1. Enzymes organize reactive groups into proximity
2. Enzymes bind transition states best (LargelyaH‡ effect)
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Support for the Proximity Model
• The rate of anhydride formation from esters and carboxylates shows a strong dependence on proximity of two reactive groups
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Support for TS Stabilization
• Structure-activity correlations in chymotrypsin substrates
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Illustration of TS Stabilization Idea:Imaginary Stickase
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How is TS Stabilization Achieved?
acid-base catalysis: give and take protonscovalent catalysis: change reaction pathsmetal ion catalysis: use redox cofactors, pKa
shifterselectrostatic catalysis: preferential
interactions with TS
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Acid-base Catalysis: Chemical Example
Consider ester hydrolysis:
R
O
C
H
3
O
R
O
C
H
3
O
O
H
H
+
R
O
O
H
+ H-OH + + CH3OH
Water is a poor nucleophile, and methanol is a poor leaving group
Aqueous hydrolysis can be catalyzed either by acids or by bases
Enzymes can do acid and base catalysis simultaneously
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Amino Acids in General Acid-Base catalysis
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•The anhydride hydrolysis reaction is catalyzed by pyridine, a better nucleophile than water (pKa=5.5).
•Hydrolysis is accelerated because of charge loss in the transition state makes pyridine a good leaving group.
Covalent Catalysis: Chemical Example
CH3O
O
CH3
O
CH3O
O
CH3O
O
H+- -+
H2O
slow + 2
CH3O
O
CH3
O
N
CH3O
O
N CH3
O
OH H
N CH3
O
OHN
CH3O
O
H+
..fast
-+ +
..
+
-
-+..
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Covalent Catalysis: In Enzymes• Proteases and peptidases
– chymotrypsin, elastase, subtilisin– reactive serine nucleophile
• Some aldehyde dehydrogenase– glyceraldehyde-3-phosphate dehydrogenase– reactive thiolate nucleophile
• Aldolases and decarboxylases– amine nucleophile
• Dehalogenases– carboxylate nucleophile
N
OH
ON
S
ON O
NH2
N O
O
O-
-